This invention relates to a method for chemically debriding abnormal damaged or necrotic tissue.
The treatment topically of traumatized or pathological areas of the body having abnormal ischemic tissue around or covering a lesion is often hampered by the fact that the ischemic tissue presented by the affected area provides pathological surface presented by the affected area provides an effective barrier to natural healing process or the healing agent employed from normal tissue to thereby initiate the healing process. In such cases, physicians sometimes resort to the very painful task of manually debriding the abnormal tissue or covering the area with bandages soaked in medication to prevent infection while keeping the surface moist. Both of these approaches have obvious limitations and pose well-known problems. There therefore is a long standing need for an effective chemical debriding agent. There is also a need for a non-toxic, nonallergenic bacteriostat and fungistat which is also effective in promoting the normal healing of traumatized or pathological epithelium by suppressing infection and/or the natural inflammatory process.
The compositions of this invention comprise biphenamine (.beta.-diethylaminoethyl 3-phenyl-2-hydroxybenzoate) base or pharmaceutically acceptable acid addition salt thereof. Salts of this compound are known to have a variety of activities, including local anesthetic (U.S. Pat. No. 1,976,922); treatment of seborrhea capitis in a shampoo (U.S. Pat. No. 3,123,531); as well as antihistaminic and bactericidal activity and fungicidal properties (U.S. Pat. No. 2,594,350; Report Annual Meeting So. Med. Assoc., Nov. 6, 1961).
Biphenamine hydrochloride has been sold as a 1% ointment, under the trademark "Melsaphine," as a topical anesthetic agent possessing bactericidal, fungicidal and antihistamine properties and as a 1% aqueous shampoo under the trademark "Alvinine," Federal Register, Vol. 34, No. 189, page 153, Oct. 2, 1969. See also U.S. Pat. No. 3,123,531.
Although its use in a shampoo for treating seborrhea and related conditions is claimed in U.S. Pat. No. 3,123,531, nothing was known concerning its ability to promote the healing of traumatized or pathological epithelium.
The topical compositions employed in the method of this invention preferably comprise, when the lesion is epithelial, an amount of a skin penetrant, e.g., DMSO (dimethyl sulfoxide) or propylene glycol, which by itself has no debriding or wound healing enhancement effects, at least in the amount employed. U.S. Pat. Nos. 3,551,554 and 3,711,602 disclose that DMSO is effective as an agent for enhancing tissue penetration of physiologically active agents. U.S. Pat. No. 3,549,770 discloses (Example 36) the topical application of a mixture of acetylsalicylic acid and DMSO is more effective than DMSO alone to relieve the pain and muscle spasm of rheumatoid spondylitis. See also U.S. Pat. Nos. 3,711,602; 3,711,606; and 3,743,727 and references cited therein. These patents disclose that the tissue penetration of physiologically active compounds, inter alia, steroidal agents and certain antimicrobial agents, can be enhanced by DMSO. U.S. Pat. No. 3,740,420 discloses DMSO compositions for topical administration containing thickening agents.
The foregoing patents disclose that concentrations of DMSO of 10% by weight and above can effect penetration of such agents through various mucous membrane barriers and that concentrations of 50% by weight and above are effective to achieve penetration thereof through the skin. DMSO is also known to enhance the antperspirant activity astringent of aluminum, zinc and zirconium salts (U.S. Pat. No. 3,499,961).
DMSO has been disclosed as useful for treating a variety of pathological conditions. U.S. Pat. No. 3,549,770 discloses topical application as a particularly advantageous route. This patent claims methods of relieving the signs and symptoms of tissue inflammation; of vascular insufficiency in the blood and lymph circulatory system; of respiratory distress; of arthritis and a method of promoting tissue repair, by administering an effective amount of DMSO, preferably topically. Dosages as low as 0.01 g/kg and up to 1.0 g/kg per day and sometimes higher dosages are contemplated with 0.1-0.2 g/kg individual doses being average. Higher concentrations of DMSO, such as at least 25% and more often at least about 50% are preferred for topical application. Treatment of pain with such solutions of DMSO, preferably by direct application to the involved area, is expressly contemplated. In one example (Example 27) the pain associated with skin abrasion was relieved with 15% DMSO in isotonic saline. 10% to 90% water solutions of DMSO, preferably 20% to 40%, in water, alcohol or glycerine are useful for topical application to the mucous membranes of the body although ". . . lower concentrations of DMSO say down to 3% by weight may be useful in some instances."
The use of DMSO as an ataratic agent is disclosed in U.S. Pat. No. 3,790,682. Pharmaceutical compositions containing DMSO and thickening agents are disclosed in U.S. Pat. No. 3,740,420, along with their use to treat and repair damaged tissue, as an anti-inflammatory agent, as an analgesic agent, as a muscle relaxant, as an agent for treating vascular insufficiency, and relieve the signs and symptoms of certain specific syndromes, viz., respiratory distress, arthritis and burns. None of the foregoing references disclose or suggest that chemical debriding can be achieved with low concentration of DMSO, e.g., topically on the skin at concentrations below 10%, although U.S. Pat. No. 3,549,770 discloses (Col. 10, lines 42-49) that for pharyngitis or hiccups, the subject may gargle with a more dilute aqueous solution, e.g., containing 1% or preferably 10% by weight of DMSO, and (Col. 28, lines 44-56) that concentrations of DMSO down to 3% by weight may be useful in some instances, with 10% to 90% water solutions being particularly suitable. The use of DMSO topically to promote the healing of traumatized or pathological epithelium at concentrations below 10% by weight is not suggested in the prior art. Moreover, I have found that low concentrations of DMSO or propylene glycol alone have little if any healing effect topically upon traumatized or pathological epithelium.